Water Processable N-Type Organic Semiconductor

The present invention concerns a water-processable n-type semiconductor comprised of polyvinylpyrrolidone (PVP), carbon nanotubes (CNTs) and poly(ethyleneimine) (PEI). The semiconductors are prepared by providing PVP and CNTs in a hydrophilic slurry and dispersing therein small amounts of PEI

DNA methylation analysis by digital bisulfite genomic sequencing and digital MethyLight

Alterations in cytosine-5 DNA methylation are frequently observed in most types of human cancer. Although assays utilizing PCR amplification of bisulfite-converted DNA are widely employed to analyze these DNA methylation alterations, they are generally limited in throughput capacity, detection sensitivity, and or resolution. Digital PCR, in which a DNA sample is analyzed in distributive fashion over multiple reaction chambers, allows for enumeration of discrete template DNA molecules, as well as sequestration of non-specific primer annealing templates into negative chambers, thereby increasing the signal-to-noise ratio in positive chambers. Here, we have applied digital PCR technology to bisulfite-converted DNA for single-molecule high-resolution DNA methylation analysis and for increased sensitivity DNA methylation detection. We developed digital bisulfite genomic DNA sequencing to efficiently determine single-basepair DNA methylation patterns on single-molecule DNA templates without an interim cloning step. We also developed digital MethyLight, which surpasses traditional MethyLight in detection sensitivity and quantitative accuracy for low quantities of DNA. Using digital MethyLight, we identified single-molecule, cancer-specific DNA hypermethylation events in the CpG islands of RUNX3, CLDN5 and FOXE1 present in plasma samples from breast cancer patients

Gamma radiation survey of the LDEF spacecraft

The retrieval of the Long Duration Exposure Facility spacecraft in January 1990 after nearly six years in orbit offered a unique opportunity to study the long term buildup of induced radioactivity in the variety of materials on board. We conducted the first complete gamma-ray survey of a large spacecraft on LDEF shortly after its return to earth. A surprising observation was the Be-7 activity which was seen primarily on the leading edge of the satellite, implying that it was picked up by LDEF in orbit. This is the first known evidence for accretion of a radioactive isotope onto an orbiting spacecraft. Other isotopes observed during the survey, the strongest being Na-22, are all attributed to activation of spacecraft components. Be-7 is a spallation product of cosmic rays on nitrogen and oxygen in the upper atmosphere. However, the observed density is much greater than expected due to cosmic-ray production in situ. This implies transport of Be-7 from much lower altitudes up to the LDEF orbit

NEOTωIST: A relatively Inexpensive Kinetic Impactor Demonstration Mission Concept

Mission concept: NEOTωIST stands for Near-Earth Object Transfer of angular momentum (ω∙I) Spin Test, and is a concept for a kinetic impactor demonstration mission, which aims to change the spin rate of an asteroid by impacting it off-center (Drube et al. 2016, Engel et al. 2016). The change would be measured by means of lightcurve measurements with Earth-based telescopes. In contrast to most other kinetic impactor demonstration mission concepts, NEOTωIST does not require a reconnaissance spacecraft to rendezvous with the target asteroid for orbit change and impact-effect measurements, and is therefore a relatively inexpensive alternative. The NEOTωIST mission would determine the efficiency of momentum transfer (the β-factor) during an impact, and help mature the technology required for a kinetic impactor mission, both of which are important precursor measures for a future space mission to deflect an asteroid by collisional means in an emergency impact hazard situation

The Presampler for the Forward and Rear Calorimeter in the ZEUS Detector

The ZEUS detector at HERA has been supplemented with a presampler detector in front of the forward and rear calorimeters. It consists of a segmented scintillator array read out with wavelength-shifting fibers. We discuss its desi gn, construction and performance. Test beam data obtained with a prototype presampler and the ZEUS prototype calorimeter demonstrate the main function of this detector, i.e. the correction for the energy lost by an electron interacting in inactive material in front of the calorimeter.Comment: 20 pages including 16 figure

Alterations of immune response of non-small lung cancer with azacytidine

Innovative therapies are needed for advanced Non-Small Cell Lung Cancer (NSCLC). We have undertaken a genomics based, hypothesis driving, approach to query an emerging potential that epigenetic therapy may sensitize to immune checkpoint therapy targeting PD-L1/PD-1 interaction. NSCLC cell lines were treated with the DNA hypomethylating agent azacytidine (AZA - Vidaza) and genes and pathways altered were mapped by genome-wide expression and DNA methylation analyses. AZA-induced pathways were analyzed in The Cancer Genome Atlas (TCGA) project by mapping the derived gene signatures in hundreds of lung adeno (LUAD) and squamous cell carcinoma (LUSC) samples. AZA up-regulates genes and pathways related to both innate and adaptive immunity and genes related to immune evasion in a several NSCLC lines. DNA hypermethylation and low expression of IRF7, an interferon transcription factor, tracks with this signature particularly in LUSC. In concert with these events, AZA up-regulates PD-L1 transcripts and protein, a key ligand-mediator of immune tolerance. Analysis of TCGA samples demonstrates that a significant proportion of primary NSCLC have low expression of AZA-induced immune genes, including PD-L1. We hypothesize that epigenetic therapy combined with blockade of immune checkpoints - in particular the PD-1/PD-L1 pathway - may augment response of NSCLC by shifting the balance between immune activation and immune inhibition, particularly in a subset of NSCLC with low expression of these pathways. Our studies define a biomarker strategy for response in a recently initiated trial to examine the potential of epigenetic therapy to sensitize patients with NSCLC to PD-1 immune checkpoint blockade

Identification of a panel of sensitive and specific DNA methylation markers for squamous cell lung cancer

<p>Abstract</p> <p>Background</p> <p>Lung cancer is the leading cause of cancer death in men and women in the United States and Western Europe. Over 160,000 Americans die of this disease every year. The five-year survival rate is 15% – significantly lower than that of other major cancers. Early detection is a key factor in increasing lung cancer patient survival. DNA hypermethylation is recognized as an important mechanism for tumor suppressor gene inactivation in cancer and could yield powerful biomarkers for early detection of lung cancer. Here we focused on developing DNA methylation markers for squamous cell carcinoma of the lung. Using the sensitive, high-throughput DNA methylation analysis technique MethyLight, we examined the methylation profile of 42 loci in a collection of 45 squamous cell lung cancer samples and adjacent non-tumor lung tissues from the same patients.</p> <p>Results</p> <p>We identified 22 loci showing significantly higher DNA methylation levels in tumor tissue than adjacent non-tumor lung. Of these, eight showed highly significant hypermethylation in tumor tissue (p < 0.0001): GDNF, MTHFR, OPCML, TNFRSF25, TCF21, PAX8, PTPRN2 and PITX2. Used in combination on our specimen collection, this eight-locus panel showed 95.6% sensitivity and specificity.</p> <p>Conclusion</p> <p>We have identified 22 DNA methylation markers for squamous cell lung cancer, several of which have not previously been reported to be methylated in any type of human cancer. The top eight markers show great promise as a sensitive and specific DNA methylation marker panel for squamous cell lung cancer.</p

Immunogenic cell death pathway polymorphisms for predicting oxaliplatin efficacy in metastatic colorectal cancer

Background Immunogenic cell death (ICD) is a tumor cell death involving both innate and adaptive immune responses. Given published findings that oxaliplatin, but not irinotecan, drives ICD, we investigated whether single nucleotide polymorphisms (SNPs) in the ICD pathway are associated with the efficacy of oxaliplatin-based chemotherapy in metastatic colorectal cancer (mCRC). Methods Two randomized clinical trials data were analyzed: discovery cohort, FOLFOX/bevacizumab arm (MAVERICC); validation cohort, FOLFOXIRI/bevacizumab arm (TRIBE); and two control cohorts, FOLFIRI/bevacizumab arms (both trials). Genomic DNA extracted from blood samples was genotyped. Ten SNPs in the ICD pathway were tested for associations with clinical outcomes. Results In total, 648 patients were included. In the discovery cohort, three SNPs were significantly associated with clinical outcomes in univariate analysis: CALR rs1010222 with progression-free survival (G/G vs any A, HR=0.61, 95% CI 0.43-0.88), ANXA1 rs1050305 with overall survival (OS) (A/A vs any G, HR=1.87, 95% CI 1.04-3.35), and LRP1 rs1799986 with OS (C/C vs any T, HR=1.69, 95% CI 1.07-2.70). Multivariate analysis confirmed the trend, but statistical significance was not reached. In the validation cohort, ANXA1 rs1050305, and LRP1 rs1799986 were validated to have the significant associations with clinical outcome. No significant associations of these SNPs were observed in the two control cohorts. Treatment-by-SNP interaction test confirmed the predictive values. Conclusions The predictive utility of ICD-related SNPs for the efficacy of oxaliplatin-based chemotherapy was demonstrated, warranting further validation studies to be translated into personalized treatment strategies using conventional cytotoxic agents in mCRC